This invention relates to a process for making vicinal difluoro aromatics using a reducing agent in the presence of various bases. Also, conditions were found to allow making halogen-substituted 1,2-difluoronaphthalenes in high yields. Vicinal difluoro aromatics, e.g., halogen-substituted 1,2-difluoronaphthalenes may be used as intermediates for liquid crystal materials.
Aromatic compounds, especially naphthalene derivatives bearing fluorine atoms on adjacent (i.e., vicinal) carbons, have been found to be useful as liquid crystal materials or their intermediates. They are typically made by a multi-step process, starting from the aromatic amine via a fluoro-dediazoniation process (N. Yoneda and T. Fukuhara, Tetrahedron, vol. 52, No. 1 (1996), pages 23-36). No simple methods are known for producing vicinal difluoro aromatic compounds. Methods for defluorinating highly fluorinated compounds are known, but none of the methods has been shown to produce vicinal difluoro compounds in high yield. For example, C. Hu et al., Journal of Fluorine Chemistry, vol. 48 (1990), pp. 29-35 disclose a method of synthesizing perfluoroaromatics, such as tetradecafluorobicyclo(4.4.0)dec-1(2),6(7)-diene and perfluorotetralin, by defluorination of hexadecafluorobicyclo(4.4.0)dec-1(6)-ene in an aprotic solvent using activated zinc powder as a reagent. The extent of defluorination depended on the polarity of the aprotic solvent used.
J. Burdon and I. W. Parsons, Journal of Fluorine Chemistry, vol. 13 (1979), pages 159-162, disclose the formation of 2,5-difluorothiophen by pyrolysis of 2,2,5,5-tetrafluoro-3-thiolen over sodium fluoride.
Sergey S. Laev and Vitalii D. Shteingarts, Journal of Fluorine Chemistry, vol. 96 (1999) pp. 175-185, disclose the reductive dehalogenation of polyfluoroarenes by zinc in ammonium hydroxide. In the reaction, hydrogen atoms replace fluorine atoms in the polyfluoroarenes.
JP 2001-10995A to Ogawa et al. describes a four-step process for synthesis of vicinal difluoro aromatic compounds involving fluorination of a hydroxy aromatic compound to form a tetrafluoro intermediate in two steps followed by hydrogenation and defluorination under basic conditions. This reference also discloses reduction of a difluoroketone intermediate with aluminum isopropoxide and then base-catalyzed dehydrohalogenation to form a difluoro aromatic compound. A third method involves reaction of the difluoroketone with lithium aluminum hydride to form a fluoroepoxide, addition of HF, and elimination of water to give a vicinal difluoro aromatic compound. The best overall yield shown is <50%.
JP2001-354600 to Kusunoki et al. discloses a process for making 6-bromo-1,2-difluoronaphthalene from 6-bromo-2-hydroxynaphthalene. The first step involves reaction of the substrate with SELECTFLUOR® fluorinating reagent to form 6-bromo-1,1-difluoro-1H-naphthalene-2-one in 95% yield. In the second step, the difluoro intermediate is fluorinated with DAST to form 6-bromo-1,1,2,2-tetrafluoro-1,2-dihydronaphthalene in 72% yield. Finally, the tetrafluoro intermediate is defluorinated using 5% Rh/C to give 6-bromo-1,2-difluoronaphthalene in 69% yield. The overall yield is only 47%.
JP2002-201145 to Yokooji et al. discloses a process for fluorinating hydroxynaphthalenes with 5% fluorine in nitrogen. Fluorination of 6-bromo-2-hydroxynaphthalene gives only 45% 6-bromo-1-fluoro-2-hydroxynaphthalene and 10% 6-bromo-1,1-difluoro-1H-naphthalene-2-one.
The parent U.S. Pat. No. 6,455,744 B1 to Lal et al. discloses a three-step process for making 1,2-difluoronaphthalenes from 2-hydroxynaphthalenes. Example 11 of the patent shows that after the treatment of 6-bromo-1,1,2,2-tetrafluoro-1,2-dihydronaphthalene with zinc in THF and NH4OH, debromination is observed and 1,2-difluoronaphthalene is produced; i.e., bromine is removed from 6-bromo-1,1,2,2-tetrafluoro-1,2-dihydronaphthalene as well as two fluorines.
Despite the foregoing developments, it is desired to provide additional processes for making vicinal difluoro aromatics, e.g., halogenated vicinal difluoro aromatic compounds in high yields.
All references cited herein are incorporated herein by reference in their entireties.